Pulse pressure is associated with plasma amyloid-β transport dysfunction

OBJECTIVE: Increased pulse pressure (PP) has been implicated in the development and progression of Alzheimer's disease in middle-aged and elderly adults. Considering the close relationship between peripheral amyloid-β clearance and brain amyloid-β deposition, we investigated the potential association between PP and plasma amyloid-β transport function. METHODS: In this cross-sectional study, a total of 1118 participants underwent a health assessment and quantification of plasma amyloid-β and amyloid-β transporter expression. Relationships between plasma levels of amyloid-β1-40, amyloid-β1-42, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), soluble receptor for advanced glycation end products (sRAGE), and PP were determined using multiple linear regressions. RESULTS: PP was a significant determinant of amyloid-β1-40 level (β = 0.059, P = 0.036) and log-transformed sRAGE (β = -0.002, P = 0.029) independent of age, sex, body mass index, pulse rate, mean arterial pressure, blood glucose, blood lipids, lifestyle, and medical history. Additionally, log-transformed soluble low-density lipoprotein receptor-related protein-1 and log-transformed sRAGE were positively associated with plasma amyloid-β1-40 level (β = 3.610, P < 0.001; β = 2.573, P = 0.001). Similar associations were observed between log-transformed sRAGE and plasma amyloid-β1-42 level (β = 1.350, P = 0.022). CONCLUSION: An elevation in PP is associated with increased plasma amyloid-β1-40 and decreased log-transformed sRAGE among individuals not taking antihypertensive medication. The underlying mechanism of this effect may be relevant to peripheral amyloid-β clearance.